Facile One-pot conversion of aldehydes into amides

Article abstract of DOI:10.1080/00397910903219443

A facile one-pot synthesis of amides from aldehydes has been developed. This tandem process involves the formation of a nitrile intermediate obtained from the reaction of an aldehyde with hydroxylamine hydrochloride in dimethylsulfoxide at 100°C and the subsequent treatment of the nitrile with basic hydrogen peroxide. The resulting amide products were produced in good yields (67-95%) and purity (>95%). Copyright

Full text of DOI:10.1080/00397910903219443

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Facile One-Pot Conversion of Aldehydes
into Amides
Samuel T. Chill a & Robert C. Mebane a
a Department of Chemistry, University of Tennessee at Chattanooga,
Chattanooga, Tennessee, USA
Published online: 08 Jun 2010.
To cite this article: Samuel T. Chill & Robert C. Mebane (2010) Facile One-Pot Conversion of
Aldehydes into Amides, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 40:13, 2014-2017, DOI: 10.1080/00397910903219443
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Synthetic Communications1, 40: 2014–2017, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903219443
FACILE ONE-POT CONVERSION OF ALDEHYDES
INTO AMIDES
Samuel T. Chill and Robert C. Mebane
Department of Chemistry, University of Tennessee at Chattanooga,
Chattanooga, Tennessee, USA
A facile one-pot synthesis of amides from aldehydes has been developed. This tandem
process involves the formation of a nitrile intermediate obtained from the reaction of an
aldehyde with hydroxylamine hydrochloride in dimethylsulfoxide at 100ꢀC and the
subsequent treatment of the nitrile with basic hydrogen peroxide. The resulting amide
products were produced in good yields (67–95%) and purity (>95%).
Keywords: Aldehyde; amide; hydrogen peroxide; nitrile; tandem reaction
Nitriles are versatile synthetic intermediates because they can be transformed into a
variety of other functional groups.[1,2] One such transformation is the selective
hydrolysis of nitriles into amides.[3] In part because of their unique electronic and
structural properties,[4] amides are particularly important functional groups and
are found in a number of natural products, polymers, and pharmaceuticals. Thus,
methods for preparing amides are highly desirable.
Recently,[5] we described a convenient one-pot synthesis of nitriles from alde-
hydes using hydroxylamine hydrochloride in dimethylsulfoxide (DMSO) at 100ꢀC.
We have now extended this synthetic methodology to the one-pot conversion of
aldehydes into amides and report our findings herein.
The experimental procedure for the one-pot conversion of aldehydes to amides
is simple and straightforward and affords amides in good isolated yields (Table 1).
As an illustrative example, octanal (2.0 mmol) was added to a solution of hydroxy-
lamine hydrochloride (3.8 mmol) in DMSO (4 mL), and the resulting reaction sol-
ution was stirred and heated for 30 min in a sand bath maintained at 100ꢀC.
Upon removal of the sand bath, but while still hot, aqueous sodium hydroxide
(1 mL of 5.68 M, 5.68 mmol) was slowly added to the reaction mixture over a
1-min period with stirring, followed by the slow and careful addition of 30%
hydrogen peroxide (2.5 mL) over a 5-min period. After stirring for 1 min, the reac-
tion mixture was extracted with ether (4 Â 20 mL), and the combined ether layers
were washed with water (4 Â 20 mL) and dried (MgSO4). Removal of the ether
Received April 13, 2009.
Address correspondence to Robert C. Mebane, Department of Chemistry, #2252, University of
Tennessee at Chattanooga, 615 McCallie Ave., Chattanooga, TN 37403-2598, USA. E-mail:
robert-mebane@utc.edu
2014

ONE-POT CONVERSION OF ALDEHYDES INTO AMIDES
2015
Table 1. Facile one-pot synthesis of amides from aldehydes
Entry
1
Aldehyde
Amide
Yield (%)a Timea
84
30
2
3
4
94
95
88
30
30
30
5
87
60
6
7
70
90
95
90
86
67
60
60
60
30
60
8
9
10
11
30
(Continued )

2016
S. T. CHILL AND R. C. MEBANE
Table 1. Continued
Entry
12
Aldehyde
Amide
Yield (%)a Timea
84
70
30
60
13
aIsolated yields.
bTime for complete conversion to amide.
solvent by rotary evaporation and high vacuum gave octanamide as a white solid
1
(0.231 g, 80% yield). The H and 13C NMR spectra and the mass spectra of the iso-
lated octanamide were identical to literature spectra.[6]
Although no mechanistic studies were performed, it seems reasonable that this
tandem conversion of an aldehyde to an amide involves two steps. First, the forma-
tion of an aldoxime followed by its dehydration gives a nitrile, and second, the nitrile
is selectively hydrolyzed to an amide by the basic hydrogen peroxide, as fully
described by Wiberg.[7]
As seen in Table 1, the reaction is general for the preparation of both aliphatic
and aromatic amides. The amides prepared in this study were confirmed by compari-
son of 1H and 13C NMR spectra and mass spectra with authentic samples. Further-
more, the 1H and 13C NMR spectra of the amide products indicated that the product
purities were greater than 95%.
In conclusion, we have demonstrated that aldehydes can be readily converted
into amides by heating (100ꢀC) the aldehydes in DMSO containing hydroxylamine
hydrochloride, followed by selective hydrolysis of the subsequent nitrile with basic
hydrogen peroxide. This one-pot, tandem process does not involve expensive or
hazardous materials and should offer an attractive alternative to recently described
procedures for converting aldehydes into amides, including the TerpyRu(PPh3)Cl2-
catalyzed rearrangement of aldoximes to amides,[8] the metal-free oxidative amina-
tion of aromatic aldehydes with tert-butyl hydroperoxide,[9] the treatment of
aldehydes with iodine in aqueous ammonia followed by hydrogen peroxide,[10,11]
the rhodium-catalyzed oxidative amination of aldehydes with N-methylmorpholine
N-oxide,[12] and the treatment of aldehydes with hydroxylamine hydrochloride=
wet alumina=methanesulfonyl chloride.[13]
ACKNOWLEDGMENTS
The authors gratefully acknowledge financial support from the Research
Corporation, the University of Chattanooga Foundation, and the Grote Chemistry
Fund.

ONE-POT CONVERSION OF ALDEHYDES INTO AMIDES
2017
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